Advances in hardware and molecular design of polarizing agents for dynamic nuclear polarization [Elektronische Ressource] / von Björn Christian Dollmann

Sujets

• Physik

Informations

• Publié par: johannes_gutenberg-universitat_mainz
• Publié le: 01 janvier 2010
• Nombre de lectures: 15
• Langue: English
• Poids de l'ouvrage: 16 Mo

Extrait

Advances in Hardware and
Molecular Design of Polarizing Agents for
Dynamic Nuclear Polarization
Dissertation zur Erlangung des Grades
,,Doktor der Naturwissenschaften"
im Promotionsfach Physik
am Fachbereich Physik, Mathematik und Informatik
der Johannes Gutenberg-Universit at in Mainz
von
Bj orn Christian Dollmann
geboren in Mainz
Mainz 2010Dekan:
1. Berichterstatter:
2. Berich
Tag der mundlic hen Prufung: 29. November 2010Contents
Contents
1. Introduction 1
2. Theoretical Background 3
2.1. NMR Fundamentals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2. EPR Ftals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
2.3. Dynamic Nuclear Polarization . . . . . . . . . . . . . . . . . . . . . . . . . 20
3. Technical Aspects of the Mobile Set-up 37
3.1. Experimental Set-up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.2. Halbach Magnet versus Electromagnet . . . . . . . . . . . . . . . . . . . . 39
3.3. Shimming of a Halbach Magnet . . . . . . . . . . . . . . . . . . . . . . . . 42
3.4. DNP Probeheads . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
3.5. Implementation of LabVIEW . . . . . . . . . . . . . . . . . . . . . . . . . 49
4. DNP Performance of the Probeheads 51
4.1. CUBOID Probehead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
4.2. PH1004 Probehead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
4.3. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
5. Overhauser-type DNP Performance of Polarizing Agents 57
5.1. TEMPOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.2. Spin-Labeled Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
5.3. Thermoresponsive Spin-Labeled Hydrogel . . . . . . . . . . . . . . . . . . 76
5.4. Summary - Polarizing Agents . . . . . . . . . . . . . . . . . . . . . . . . . 83
6. Solid-State DNP Performance of Polarizing Agents 86
6.1. TEMPOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
6.2. Spin-Labeled Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
6.3. Thermoresponsive Spin-Labeled Hydrogel . . . . . . . . . . . . . . . . . . 104
6.4. Summary - Solid-State DNP . . . . . . . . . . . . . . . . . . . . . . . . . . 106
7. Hyperpolarization of Hetero Nuclei 108
7.1. Hexa uorobenzene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
197.2. DNP of a Dissolved F Containing Molecule . . . . . . . . . . . . . . . . 115
137.3. C-Enriched Urea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
i7.4. Summary - Hyperpolarization of Hetero Nuclei . . . . . . . . . . . . . . . 122
8. Conclusion 124
Appendix 128
A. Appendix - Methods 128
A.1. Determination of Unknown Radical Concentrations . . . . . . . . . . . . . 128
A.2. CW EPR Line Shape Analysis . . . . . . . . . . . . . . . . . . . . . . . . 128
A.3. ESE-Detected Line Shape Analysis . . . . . . . . . . . . . . . . . . . . . . 130
A.4. DEER Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
A.5. Electron spin-lattice determination at room temperature . . . . . . . . . . 130
A.6. DNP Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
A.7. Determination of the Quality Factor of the EPR Probeheads . . . . . . . 132
B. Materials - Polarizing Agents, Solvents and Used Molecules 134
B.1. TEMPO Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
B.2. Spin-Labeled Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
B.3. SL-Hydrogel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
B.4. Solvents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
B.5. Solutes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
C. Matlab Scripts 143
C.1. Enhancement and Power Dependence . . . . . . . . . . . . . . . . . . . . 143
C.2. Magnetic Field Sweep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
Bibliography 1521. Introduction
1. Introduction
Nuclear magnetic resonance (NMR) is a versatile technique relying on spin-bearing nu-
1,2clei. Since its discovery more than 60 years ago, NMR and related techniques have
become indispensable tools with innumerable applications in physics, chemistry, biology
and medicine. One of the main obstacles in NMR is its notorious lack of sensitivity,
which is due to the minuscule energy splitting caused by the nuclear spins at room tem-
perature. Even for proton spins, which possess the largest magnetogyric ratio, the degree
5of polarization in the highest available magnetic elds (24 T) is only 7 10 . Appro-
priately, the inherent low polarization allows for a theoretical sensitivity enhancement
4of more than 10 . In the eld of magnetic resonance imaging (MRI) this issue becomes
even more severe as the magnetic elds of whole-body tomographs do not reach the eld
strengths of magnets for NMR spectroscopy. Accordingly, MRI is mainly restricted to
13the imaging of water protons and the application of C (or other low nuclei) NMR
spectroscopy and imaging for clinical diagnosis has been constrained by the extremely
long imaging and spectroscopy acquisition times that are required to obtain high signal-
13to-noise ratios under physiological conditions (low natural abundance of C and low
13concentration of C-compounds).
Due to this potential sensitivity increase which can open up completely new research
elds in NMR spectroscopy and imaging, several hyperpolarization techniques have been
developed to overcome this drawback of NMR. The hyperpolarization techniques can be
divided into two sub-groups: (i) Chemistry-based polarization methods like e.g. para-
3{5hydrogen induced polarization (PHIP) and photochemically induced dynamic nuclear
6{8polarization (Photo-CIDNP). (ii) Physics-oriented polarization methods like e.g. op-
9,10 11{15tical pumping of noble gases and dynamic nuclear p (DNP) which was
used in this thesis.
DNP is a polarization technique which transfers the polarization of unpaired electron
spins to the surrounding nuclei by microwave irradiation. The theoretical enhancement
is given by the ratio of the magnetogyric ratios of the electron spin and a nuclear spin.
1 19 13This ratio for proton ( H), uorine ( F) and carbon ( C) nuclei is E 660, E 700
and E 2600, respectively. The most characteristic feature and signi cant drawback
are the presence of unpaired electrons in the sample which have to be added if they are
not inherent to the sample. On the other hand, DNP is not limited to a special molecule
or nucleus which makes it remarkably versatile.
With respect to the possible NMR signal enhancements, especially for low nuclei, many
11. Introduction
new experiments in physics, chemistry, biology and medicine emerge. Particularly in
medicine new diagnostic pathways can be taken by utilizing hyperpolarized substances
13,16as active contrast agent. For example, the metabolism of the physiological rele-
16,17vant substance pyruvate could be examined via MRI. Thus, further development of
technical components and suitable polarizing agents for Overhauser-type and solid-state
DNP are of high importance.
So far, only few medical applications are based on the DNP technique. Nevertheless,
this thesis deals exclusively with the technical development of a mobile DNP polarizer
and the design of suitable polarizing agents for DNP and prospective medical appli-
cations. After this introductory Chapter, the basic theoretical background is given to
comprehend the experimental results of the following parts. The rst part will discuss
the technical improvements which could be achieved regarding the mobile DNP polar-
izer. These improvements comprise the realization of a homogeneous Halbach magnet,
the implementation of an automated experiment control and the construction of new
probeheads. In the Chapters 3 and 4 the importance of these technical improvements
will be demonstrated.
In the main part of this thesis the DNP performance of new polarizing agents is pre-
sented and compared to a commonly used polarizing agent. The DNP performance was
tested at physiological and cryogenic temperatures. Appropriately, Chapter 5 deals with
the Overhauser-type DNP and Chapter 6 with the solid-state DNP. These two Chap-
ters particularly focus on the biocompatibility and removal of polarizing agents which is
an important issue concerning the medical application of hyperpolarized substances via
DNP.
In Chapter 7 the feasibility of DNP experiments on hetero nuclei in the mobile set-up,
working at 0.35 T, is demonstrated. Along with the achieved NMR signal enhancements
by DNP, the measurements prove the possibility of a fast and reliable NMR detection
and nuclear spin-lattice relaxation time determination of biomolecules by using DNP.
This experiment shows the potential of DNP, especially at X-band, when it comes to
the polarization of nuclei with a very low magnetogyric ratio.
22. Theoretical Background
2. Theoretical Background
This Chapter introduces the basic knowledge to understand and interpret the data and
results summarized in the thesis. The presented theoretical fundamentals comprise the
11,12,18topics introduced and explained in many